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© 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

The expression of Merlin tumor suppressor protein encoded by Neurofibromin 2 (NF2) gene is remarkably decreased in metastatic breast cancer tissues. In order to recapitulate clinical evidence, we generated a unique, conditional Nf2‐knockout (Nf2−/−) mouse mammary tumor model. Merlin‐deficient breast tumor cells and Nf2−/− mouse embryonic fibroblasts (MEFs) displayed a robustly invasive phenotype. Moreover, Nf2−/− MEFs presented with notable alterations in redox management networks, implicating a role for Merlin in redox homeostasis. This programmatic alteration resonated with pathways that emerged from breast tumor cells engineered for Merlin deficiency. Further investigations revealed that NF2‐silenced cells supported reduced activity of the Nuclear factor, erythroid 2 like 2 antioxidant transcription factor, concomitant with elevated expression of NADPH oxidase enzymes. Importantly, mammary‐specific Nf2−/− in an Mouse mammary tumor virus Neu + murine breast cancer model demonstrated accelerated mammary carcinogenesis in vivo. Tumor‐derived primary organoids and cell lines were characteristically invasive with evidence of a dysregulated cellular redox management system. As such, Merlin deficiency programmatically influences redox imbalance that orchestrates malignant attributes of mammary/breast cancer.

Details

Title
Merlin deficiency alters the redox management program in breast cancer
Author
Mota, Mateus 1 ; Metge, Brandon J 1 ; Hinshaw, Dominique C 1 ; Alsheikh, Heba A 1 ; Chen, Dongquan 2 ; Samant, Rajeev S 3 ; Shevde, Lalita A 4   VIAFID ORCID Logo 

 Department of Pathology, University of Alabama at Birmingham, AL, USA 
 Division of Preventive Medicine, University of Alabama at Birmingham, AL, USA 
 Department of Pathology, University of Alabama at Birmingham, AL, USA; O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, AL, USA; Birmingham VA Medical Center, AL, USA 
 Department of Pathology, University of Alabama at Birmingham, AL, USA; O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham, AL, USA 
Pages
942-956
Section
Research Articles
Publication year
2021
Publication date
Apr 2021
Publisher
John Wiley & Sons, Inc.
ISSN
15747891
e-ISSN
18780261
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2509138156
Copyright
© 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.